title: Exercise training does not correct abnormal cardiac glycogen accumulation in the db/db mouse model of type 2 diabetes.
abstract: Substrate imbalance is a well-recognized feature of diabetic cardiomyopathy. Insulin resistance effectively limits carbohydrate oxidation, resulting in abnormal cardiac glycogen accumulation. Aims of the present study were to 1) characterize the role of glycogen-associated proteins involved in excessive glycogen accumulation in type 2 diabetic hearts and 2) determine if exercise training can attenuate abnormal cardiac glycogen accumulation. Control (db(+)) and genetically diabetic (db/db) C57BL/KsJ-lepr(db)/lepr(db) mice were subjected to sedentary or treadmill exercise regimens. Exercise training consisted of high-intensity/short-duration (10 days) and low-intensity/long-duration (6 wk) protocols. Glycogen levels were elevated by 35-50% in db/db hearts. Exercise training further increased (2- to 3-fold) glycogen levels in db/db hearts. Analysis of soluble and insoluble glycogen pools revealed no differential accumulation of one glycogen subspecies. Phosphorylation (Ser(640)) of glycogen synthase, an indicator of enzymatic fractional activity, was greater in db/db mice subjected to sedentary and exercise regimens. Elevated glycogen levels were accompanied by decreased phosphorylation (Thr(172)) of 5'-AMP-activated kinase and phosphorylation (Ser(79)) of its downstream substrate acetyl-CoA carboxylase. Glycogen concentration was not associated with increases in other glycogen-associated proteins, including malin and laforin. Novel observations show that exercise training does not correct diabetes-induced elevations in cardiac glycogen but, rather, precipitates further accumulation.
authors.affiliation: Kinesiology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Shearer
authors.forename: Karen D
authors.initials: KD
authors.lastname: Ross
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Hughey
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Johnsen
authors.forename: Dustin S
authors.initials: DS
authors.lastname: Hittel
authors.forename: David L
authors.initials: DL
authors.lastname: Severson
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D058065:Diabetic Cardiomyopathies / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005081:Exercise Therapy; D006003:Glycogen / Q000378:metabolism*; D052120:Glycogen Storage Disease Type IIb / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D054411:Receptors, Leptin / Q000235:genetics
chemical_list: D054411:Receptors, Leptin; D006003:Glycogen